Immunologic mechanisms of renal disease

Abstract

Most immune renal diseases are caused by the formation of immune complexes of antibody with either fixed glomerular antigens or exogenous non-renal antigens. Much progress has been made recently in understanding the ways by which these immune deposits form in glomeruli. Immune complex deposits of exogenous antigens may involve prior antigen localization in the glomerulus to initiate immune complex formation locally, or in situ. The type of glomerular lesion produced depends in large part on the site at which deposit formation occurs, which in turn determines what mediators of tissue injury are activated. The nature and quantity of immune reactants are also important. Subepithelial deposits may result from antibody binding to fixed epithelial cell-derived antigens or to exogenous antigens localized by direct interaction with glomerular anionic sites (cationic antigens) or with nonimmune cationic proteins bound to glomerular anionic sites (anionic antigens). Cationic antibody may also localize first, and deposits can form from subendothelial immune complex deposits dissociating to cross the GBM and re-form in a subepithelial distribution. Proteinuria induced by subepithelial immune deposit formation appears to be due to a direct effect of complement, probably involving membrane attack complexes, and independent of inflammatory cells. Intramembranous deposits form from anti-GBM antibody reacting with intrinsic GBM antigens. Subendothelial and mesangial deposits appear not to involve fixed antigens. Rather, they represent immune complexes containing exogenous antigens and antibody to the antigens. These complexes may result from the passive trapping of pre-formed immune complexes from the circulation or may form in situ by several different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)